title: The involvement of CD36 in monocyte activation by antiphospholipid antibodies.
abstract: BACKGROUND
  CD36, known as a scavenger receptor, is a transmembrane glycoprotein expressed on monocytes, platelets and endothelial cells, recognizes multiple ligands, including phosphatidylserine, and regulates atherogenesis and thrombosis. The objective of this study is to investigate the possible involvement of CD36 in the pathophysiology of thrombosis in patients with antiphospholipid syndrome (APS).
  
  
  METHODS
  First, rs3765187, a missense mutation linked to CD36 deficiency, was investigated by TaqMan polymerase chain reaction (PCR) genotyping method in 819 Japanese, including 132 patients with APS, 265 with systemic lupus erythematosus (SLE) in the absence of APS, and 422 healthy subjects. Then, the involvement of CD36 in antiphospholipid antibody (aPL)-induced tissue factor (TF) expression was examined using CD36-null mice or anti-CD36. Purified IgG from patients with APS and a monoclonal phosphatidylserine-dependent antiprothrombin antibody were used in these experiments. TF expression was tested by real-time PCR and flow cytometry.
  
  
  RESULTS
  Minor allele carrier of rs3765187 was less frequent in patients with APS (3.8% p=0.032), but not in patients with SLE in the absence of APS (7.9% p=0.32), compared with healthy subjects (10.2%). The aPL-induced TF expression was significantly suppressed on peritoneal macrophages from CD36-null mice compared to wild type and significantly inhibited by anti-CD36 on human monocytes.
  
  
  CONCLUSIONS
  The gene mutation linked to CD36 deficiency was less frequent in patients with APS. The deficient or suppressed CD36 function significantly reduced aPL-induced TF expression in vitro. Taken together, in a susceptible background CD36 scavenger receptor function may be involved in the thrombotic pathophysiology in patients with APS.
authors.affiliation: Department of Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Atsumi
authors.forename: K
authors.initials: K
authors.lastname: Oku
authors.forename: O
authors.initials: O
authors.lastname: Amengual
authors.forename: H
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Fujieda
authors.forename: K
authors.initials: K
authors.lastname: Otomo
authors.forename: T
authors.initials: T
authors.lastname: Horita
authors.forename: S
authors.initials: S
authors.lastname: Yasuda
authors.forename: T
authors.initials: T
authors.lastname: Koike
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000378:metabolism*; D016736:Antiphospholipid Syndrome / Q000235:genetics / Q000503:physiopathology*; D018955:CD36 Antigens / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D006801:Humans; D007564:Japan; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000503:physiopathology; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D060888:Real-Time Polymerase Chain Reaction; D013925:Thromboplastin / Q000235:genetics; D013927:Thrombosis / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D017152:Antibodies, Antiphospholipid; D018955:CD36 Antigens; D013925:Thromboplastin
keywords: Antiphospholipid syndrome; lupus anticoagulant; scavenger receptor; thrombosis